Did you know that Severe COVID-19 can accelerate brain aging?
Written by Gala Konteva; a 3rd-year student of Biological Sciences at the University of Leeds and Neural Networks' science writer
Although COVID-19 is considered primarily a respiratory disease, neurological symptoms have been observed in many COVID-19 patients, such as loss of smell and taste, memory problems and movement disorders. Therefore, a lot of research has been focused on the effects of SARS-CoV-2, the causative pathogen of COVID-19, on the human brain. For instance, the long-lasting COVID-19 symptoms are believed to be caused not only by direct organ damage by the virus but also by brain inflammation, resulting from the infection (Frere et al., 2022). Furthermore, we now know that there is a link between severe COVID-19 and cognitive decline, as a result of impairments in the frontal cortex of the brain, which accelerates ageing (Venkataramani and Winkler, 2022).
A recent study, published 2 months ago by Mavrikaki et al., investigated the effects of severe COVID-19 on the brain to find out how the infection contributes to cognitive decline and ageing. The team used RNA sequencing to compare the gene expression profiles of brain frontal cortex samples taken from patients who had severe COVID-19 and from non-infected people. What they found was that genes involved in immune-related pathways and stress are more active in the infected individuals, whereas genes associated with cognition, memory and synaptic activity were downregulated.
This transcription pattern is actually observed in the ageing brain, therefore, they directly compared gene activity between frontal complex samples from young and old individuals and this confirmed that genes, active in the brains of the elderly are also more active in the brains of people who had suffered from severe COVID-19.
What is the reason behind these transcriptional changes in the brain?
Surprisingly, no viral RNA was detected in the frontal cortex samples taken from the patients. In general, severe COVID-19 is driven not only by viral damage to cells but by a reactive “storm” of inflammation that can damage the host tissues and organs more than the virus itself. Therefore, they speculated that these gene activity changes are caused indirectly, by neuroinflammatory processes resulting from the infection, rather than by the direct effect of the virus, such as viral infiltration of the brain. This was confirmed, as they cultured human primary neurons with inflammatory cytokines, which induced transcriptional changes similar to those seen in patients with severe COVID-19.
All this taken, their study showed that in severe COVID-19, the virus SARS-CoV-2 indirectly dysregulates gene expression in the frontal cortex by activating specific inflammatory responses, which in turn accelerates brain ageing and cognitive decline. This knowledge can be used for the development of novel therapeutics addressing cognitive decline. In addition, future research on the immune system's role in COVID-19 is crucial, as it is associated with brain ageing, and potentially treating inflammation can prevent longer-lasting damage and brain ageing in severe COVID-19 cases.
If this study interests you, feel free to go and explore the work they did by reading the paper yourself: https://www.nature.com/articles/s43587-022-00321-w
Reference list
Frere, J.J., Serafini, R.A., Pryce, K.D., Zazhytska, M., Oishi, K., Golynker, I., Panis, M., Zimering, J., Horiuchi, S., Hoagland, D.A., Møller, R., Ruiz, A., Kodra, A., Overdevest, J.B., Canoll, P.D., Borczuk, A.C., Chandar, V., Bram, Y., Schwartz, R. and Lomvardas, S. 2022. SARS-CoV-2 infection in hamsters and humans results in lasting and unique systemic perturbations post recovery. Science Translational Medicine. 14(664).
Mavrikaki, M., Lee, J.D., Solomon, I.H. and Slack, F.J. 2022. Severe COVID-19 is associated with molecular signatures of aging in the human brain. Nature Aging. 2, p.p. 1130–1137.
Venkataramani, V. and Winkler, F. 2022. Cognitive Deficits in Long Covid-19 E. G. Phimister, ed. New England Journal of Medicine. 387(19), pp.1813–1815.